DESCRIPTION: Methamphetamine dependence is a growing problem, especially in the western United States, and is strongly associated with HIV risk behaviors. We will investigate the efficacy of a novel pharmacotherapy in the treatment of methamphetamine dependence. A two phase study is proposed -- an out patient clinical trial (Phase 1 ) coupled with an inpatient cue-reactivity study (Phase 2). The project will use quantitative urine methamphetamine and amphetamine levels as measures of drug use outcome, and will evaluate the value of such quantitative measurements versus qualitative urine drug testing. The medication to be tested is isradipine, a dihydropyridine calcium channel blocker. Animal studies indicate that isradipine reduces the reinforcing and activating effects of methamphetamine. The proposed studies will test isradipine's effectiveness in two experiments, one in a human laboratory and the other in an outpatient setting. One hundred subjects will be recruited into a randomized, placebo- controlled, parallel group, 12 week outpatient clinical trial (Study Phase 1) to test the effectiveness of isradipine, as a adjunct to group therapy, in initiating abstinence or reducing the amount of methamphetamine use among patients with DSM-IV methamphetamine dependence. Outcome measures for the clinical trial will be quantitative urine methamphetamine and amphetamine concentration and self report of methamphetamine use and craving, as well as AIDS risk behaviors. Of the 100 subjects, 30 will also be recruited into a concurrent human laboratory cue reactivity study (Study Phase 2) designed to measure isradipine's efficacy in reducing methamphetamine reactivity in response to cues. The cue-reactivity study will involve overnight hospitalization and will utilize the General Clinical Research Center (GCRC) atg UCSF/San Fransisco General Hospital. Subjects will participate in the first cue reactivity session during Week 1 (the placebo/compliance week) at the start of the outpatient isradipine trial, and will return to the GCRC for the second cue reactivity session in Week 5 of treatment with isradipine or placebo. Cue reactivity outcome will be measured by subjective responses such as craving as well as physiological measurements of arousal such as autonomic changes, skin conductance, and cortisol levels. In those subjects who participate in both phases of the project, the severity of cue reactivity in Phase 2 will be correlated with amount of outpatient methamphetamine use as measured in Phase1.